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The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth.
Open accessAbstract
Expression of a p53-associated protein, Mdm-2 (murine double minute-2), can inhibit p53-mediated transactivation. In this study, overexpression of the Mdm-2 protein was found to result in the immortalization of primary rat embryo fibroblasts (REFs) and, in conjunction with an activated ras gene, in the transformation of REFs. The effect of wild-type p53 on the transforming properties of mdm-2 was determined by transfecting REFs with ras, mdm-2, and normal p53 genes. Transfection with ras plus mdm-2 plus wild-type p53 resulted in a 50% reduction in the number of transformed foci (relative to the level for ras plus mdm-2); however, more than half (9 of 17) of the cell lines derived from these foci expressed low levels of a murine p53 protein with the characteristics of a wild-type p53. These results are in contrast to previous studies which demonstrated that even minimal levels of wild-type p53 are not tolerated in cells transformed by ras plus myc, E1A, or mutant p53. The mdm-2 oncogene can overcome the previously demonstrated growth-suppressive properties of p53.
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Metadata
- Authors
- Finlay, C. A.
- Affiliations
- Princeton University (US)
- Corresponding author
- Finlay, C A
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1993-01
- Volume
- 13
- Issue
- 1
- Pages
- 301-306
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC358909
- OpenAlex
- W2137124052
- Cited by
- 311
- References
- 45
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 6 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 4 · 2012: 6
- FWCI
- 13.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca055036-03)
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- MDM2, p53, oncogenes, cell transformation, Ras, cell immortalization, rat embryo fibroblasts, growth inhibition, p53 transactivation, tumor suppressor, transformed foci
- MeSH terms
- Animals, Cell Division, Cell Transformation, Neoplastic, Neoplasm Proteins, Nuclear Proteins, Precipitin Tests, Proto-Oncogene Proteins, Proto-Oncogenes, Rats, Inbred F344, Oncogene Proteins, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, Rats, Proto-Oncogene Proteins c-mdm2
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